Association between the surfactant protein D ( SFTPD ) gene and subclinical carotid artery atherosclerosis

• Published in: Atherosclerosis Vol. 246; pp. 7 - 12
• Main Authors: Sorensen, Grith L, Bladbjerg, Else Marie, Steffensen, Rudi, Tan, Qihua, Madsen, Jens, Drivsholm, Thomas, Holmskov, Uffe
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 01.03.2016
• Subjects: Asymptomatic Diseases; Atherosclerosis; Cardiovascular; Carotid Arteries - diagnostic imaging; Carotid Artery Diseases - blood; Carotid Artery Diseases - diagnostic imaging; Carotid Artery Diseases - genetics; Carotid Intima-Media Thickness; Chi-Square Distribution; Denmark; Female; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Intima-media thickness; Linear Models; Logistic Models; Male; Middle Aged; Multivariate Analysis; Phenotype; Plaque, Atherosclerotic; Polymorphism, Single Nucleotide; Pulmonary Surfactant-Associated Protein D - blood; Pulmonary Surfactant-Associated Protein D - genetics; Risk Assessment; Risk Factors; Single nucleotide polymorphisms; Smoking - adverse effects; Surfactant protein D; Intima-media thickness; Surfactant protein D; Single nucleotide polymorphisms; Atherosclerosis
• DOI: 10.1016/j.atherosclerosis.2015.12.037
• ISSN: 0021-9150

Abstract Objective Surfactant protein D (SP-D) is a defense collectin with inflammation-modulating properties. SP-D deficiency inhibits atherosclerosis in vivo , and the circulatory SP-D levels have been previously associated with cardiovascular disease mortality. We hypothesized that plasma SP-D (pSP-D) and SP-D gene ( SFTPD ) single nucleotide polymorphisms (SNPs) are risk factors for atherosclerosis. Methods We evaluated individuals who were all 60 years old and participated in The Glostrup Population Study. Subclinical atherosclerosis was diagnosed based on the ultrasonographic measurement of intima-media thickness (IMT) and protruding plaques in the right carotid artery. Associations between cardiovascular traits and the levels of pSP-D (n = 687) or two coding SFTPD SNPs rs3088308 and rs721917 (n = 396) were investigated using multiple linear regressions and logistic regressions. Results There was no significant association between pSP-D and the presence of plaques or IMT. The SFTPD SNP rs3088308 was nominally associated with the presence of plaques, and rs721917 was nominally associated with IMT. The directions of effects of associations were markedly dependent on current smoking status. Conclusions The results do not support that pSP-D levels influence the development of subclinical atherosclerosis. However, the SFTPD SNP data support previous observations from animal studies that SP-D plays a role in the etiology of atherosclerotic disease development. The nominal significant effects are likely to be mediated by structural variant SP-D modulation of effects of tobacco smoking and are independent of pSP-D levels. The data warrant confirmation in larger cohorts.